Integrated Single-Cell Atlas Reveals Cross-Subtype Heterogeneity in Human Pulmonary Hypertension - PubMed
2 hours ago
- #single-cell RNA sequencing
- #pulmonary hypertension
- #vascular remodeling
- Study integrated single-cell RNA sequencing data to create a unified cellular atlas for pulmonary hypertension (PH), addressing fragmentation across clinical subtypes and heterogeneous processing pipelines.
- The atlas includes 235,621 cells from 64 human samples across idiopathic pulmonary arterial hypertension, systemic sclerosis-associated PH, chronic thromboembolic PH, and healthy controls, organized into 6 lineages and 58 cell states.
- Cross-subtype analysis revealed shared and subtype-specific remodeling in vascular and immune compartments, including redefined smooth muscle cell states and fibroblast-associated complement activation in idiopathic pulmonary arterial hypertension.
- System-dependent differences were noted, such as variable MHC class II activation in capillary endothelial cells between animal models and human PH, and phenotypic shifts in cultured versus native endothelial cells.
- Developed PH-Map, a multitask learning tool for rapid hierarchical cell annotation, validated for stable performance and improved computational efficiency in external cohorts.
- The atlas and PH-Map facilitate systematic cross-subtype comparisons and support reproducible annotation for downstream studies of candidate cell states and pathways.